SYSMEX R-3500, AUTOMATED RETICCULOCYTE ANALYZER, MODEL R-3500

K981950 · Sysmex Corp. · GKL · Nov 3, 1998 · Hematology

Device Facts

• Record ID: K981950
• Device Name: SYSMEX R-3500, AUTOMATED RETICCULOCYTE ANALYZER, MODEL R-3500
• Applicant: Sysmex Corp.
• Product Code: GKL · Hematology
• Decision Date: Nov 3, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5200
• Device Class: Class 2

Indications for Use

The intended use of the Sysmex R-3500 is as a fully automated reticulocyte analyzer for in vitro diagnostic use in clinical laboratories.

Device Story

The Sysmex R-3500 is an automated flow cytometry analyzer for clinical laboratories. It processes whole blood samples via four modes: sampler (auto), closed, manual, and capillary. The device aspirates, dilutes, and stains samples with Auramine-O fluorescent dye. An Argon laser illuminates the hydrodynamically focused cells; the system measures forward light scatter and fluorescence intensity. A computer algorithm performs adaptive cluster analysis on the scattergram to discriminate and enumerate reticulocytes, red blood cells, and platelets. The reticulocyte population is further categorized into low, middle, and high fluorescence ratios (LFR, MFR, HFR). The device outputs quantitative results and scattergrams to a data management system (DMS). Abnormalities are flagged for clinician review. The system includes a statistical quality control program. By providing precise reticulocyte counts and immature reticulocyte fractions, the device assists clinicians in evaluating erythropoietic activity and hematological status.

Clinical Evidence

Bench testing only. Correlation studies compared the R-3500 to the RAM-1 predicate using 487 patient samples covering healthy and pathological conditions. Results showed high correlation coefficients (r) for all parameters: RET# (0.994), RET% (0.997), RBC (0.998), IRF (0.956), LFR (0.956), MFR (0.923), HFR (0.954), and Platelets (0.994).

Technological Characteristics

Flow cytometry using Argon laser excitation and Auramine-O fluorescent staining. Hydrodynamic focusing. Parameters: RET%, RET#, RBC, IRF, LFR, MFR, HFR, PLT. Dimensions: 720x630x505 mm. Weight: 85.5 kg. Connectivity: Data Management System (DMS) with barcode reader. QC: Levy-Jennings, 15 files per parameter, 180 points per file.

Indications for Use

Indicated for in vitro diagnostic use in clinical laboratories for the automated analysis of whole blood samples to provide reticulocyte and red blood cell parameters, including RET%, RET#, RBC, IRF, LFR, MFR, HFR, and PLT.

Regulatory Classification

Identification

An automated cell counter is a fully-automated or semi-automated device used to count red blood cells, white blood cells, or blood platelets using a sample of the patient's peripheral blood (blood circulating in one of the body's extremities, such as the arm). These devices may also measure hemoglobin or hematocrit and may also calculate or measure one or more of the red cell indices (the erythrocyte mean corpuscular volume, the mean corpuscular hemoglobin, or the mean corpuscular hemoglobin concentration). These devices may use either an electronic particle counting method or an optical counting method.

Predicate Devices

• Sysmex SE/RAM-1 (K964375)
• Sysmex R-3000 (K912494)

Submission Summary (Full Text)

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### 3 1998 NOV

# 510(k) Premarket Notification Sysmex™ Automated Reticulocyte Analyzer R-3500 May 31, 1998

## I. DEVICE NAME:

Trade or Proprietary Name: Sysmex™Automated Reticulocyte Analyzer R-3500

Automated Reticulocyte Analyzer Common or Usual Name:

## II. CLASSIFICATION NAMES:

| Automated Cell Counter | 81 GKL |
|---------------------------------|--------|
| Automated Cell Dilution Device | 81 GKH |
| Computer System Integrated with | |
| Hematology Analyzers | 81 JWS |
| | |
| Related Items: | |
| Diluent: RETSHEATH | 81 GIF |
| RETSEARCH diluent | 81 GIF |
| Stain: RETSEARCH dye | 81 KJK |
| Detergent: CELLCLEAN | 81JCB |
| Calibrators: | |
| Sysmex™Latex Particle-R | 81 KSA |
| Sysmex™SCS-Ret | 81 KSA |
| Accessories: | |
| Pneumatic Unit (PU-8) | NA |
| Sampler Unit (SU) | NA |
| Slide Preparation Unit (SP-100) | 81GKJ |
| Line Controller (LC-2) | NA |
| Conveyor Unit (CVR-1) | NA |
| Rack Slider (RS) | NA |
| Start Yard (STY) | NA |
| Stock Yard (SKY) | NA |
| Extended Conveyor (EC-1) | NA |
| Turn Unit (TU-1) | NA |
| Data Entry Unit (DE-2) | NA |

## III. ESTABLISHMENT INFORMATION:

| Location | Registration Number | |
|-----------------------------------------------------------------|-------------------------------|----------------------------|
| Manufacturer Site<br>TOA Medical Electronics Co.<br>Kobe, Japan | Owner/Operator No.<br>7010360 | Manufacturer No.<br>961466 |

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Importer & Distributor Registration Number Sysmex™ Corporation 1422681 Gilmer Road 6699 RFD Long Grove, IL 60047-9596

## IV. CLASSIFICATION INFORMATION:

Automated reticulocyte instruments have been classified by the Hematology and Pathology Devices Panel as Class II devices.

The Immature Reticulocyte Fraction (IRF) Parameter is a Class III parameter that has already been cleared for all Sysmex™ R-Series Analyzers (see 510(k) submission #K971736).

## V. COMPLIANCE WITH PERFORMANCE STANDARDS:

To date, no performance standards which affect this device have been finalized under Section 514 of the Food, Drug, and Cosmetic Act.

## VI. PROPOSED LABELING:

A draft copy of the proposed labeling, Operator's Manual, Reagent Labeling and Sales Brochures are included.

### VII. SUMMARY

Complete information on the Safety and Effectiveness Summary is included in Attachment 3.

#### DESCRIPTION VIII.

The Sysmex™ R-3500 is an automated reticulocyte analyzer intended for in vitro use in clinical laboratories.

The R-3500 provides accurate and precise test results for 8 analysis parameters in whole blood. These include RET%, RET#, RBC, IRF, LFR, MFR, HFR, and PLT.

The R-3500 processes approximately 120 samples per hour and displays and prints the data for Reticulocyte number, Reticulocyte percent, Red blood cell count, Immature reticulocyte fraction, fluorescent ratios, and platelets along with representative scattergrams. Sample abnormalities are indicated by abnormal marks, flags, and error messages which appear on the DMS display screen and on the printout. This is an indication that the sample is not within the acceptable range and requires further review and investigation.

The R-3500 uses the principle of flow cytometry for reticulocyte analysis. In the instrument, a whole blood sample is automatically aspirated, diluted and stained with a fluorescent dye (Auromine-O). The sample is hydrodynamically focused into a narrow path and passed through a flow cell, where it is illuminated by an Argon laser beam. The

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cells present in the sample will fluoresce and scatter light to varying degrees. It is the analysis of the intensity of emitted fluorescent light and intensity of scattered light which allows the R-3500 analyzer to detect and enumerate reticulocytes.

A computer algorithm discriminates the different populations of cells based on the intensity of light scatter and fluorescence, and displays this on a scattergram. The red blood cells, platelets and reticulocytes are separated by means of adaptive cluster analysis of the scattergram. The reticulocyte region of the scattergram is divided into three regions based on fluorescence intensity. These areas are called the low, middle and high fluorescence ratios (LFR, MFR and HFR), and are expressed as a ratio or percentage (sum = 100) of the total reticulocyte count. The immature reticulocyte fraction (IRF) is equal to the MFR+HFR.

The R-3500 provides four modes of sample introduction: 1) Sampler (auto) Mode, 2) Closed Mode, 3) Manual Mode and 4) Capillary Mode. The Sampler mode is completely automated; closed tubes are placed in the auto mode racks, and are automatically moved through the system. Whole blood is aspirated automatically via a cap piercing system. The Closed Mode also uses the cap piercing system, but samples are analyzed one at a time. In the Manual (open) Mode, the sample tube cap is opened and the sample is aspirated through the sample probe. The Capillary Mode allows for the use of smaller volume samples such as obtained from a child. In this mode, a blood sample is diluted before analysis is performed.

Operator interface with the R-3500 is accomplished with the use of a data management system (DMS), as well as a main unit control panel keypad.

The R-3500 has a quality control (QC) program which performs statistical QC. The R-3500 maintains the reliability of analyzed data by monitoring the stability of the system (instrument and reagents) over a laboratory-defined interval. This type of QC refers to statistical calculations performed on control blood. In the QC program, QC data for each analysis parameter is obtained by analyzing control blood and storing the results in a QC file. The instrument provides 15 QC files for each test parameter, including 2 troubleshooting (alignment) parameters. Each OC file stores the latest 180 points.

There are disposables and consumables associated with the system which are required for its normal operation.

To keep the R-3500 in optimal operating conditions, periodic maintenance is required.

### IX. SUBSTANTIAL EQUIVALENCE:

The R-3500 is substantially equivalent in intended use and technological characteristics to the Sysmex™ SE/RAM-1 and Sysmex™ R-3000. A summary of the comparative features is presented in Table 1.

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## Table 1 Comparative Features between R-3500 and RAM-1/R-3000

| Features | R-3500 | SE/RAM-1<br>K964375 | R-3000<br>K912494 |
|----------------------------|--------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------|
| FDA Clearance Date | | Mar. 13, 1997 | Sept. 10, 1991 |
| Intended Use | Automated<br>reticulocyte counter<br>for in vitro diagnostic<br>use in clinical<br>laboratories | Automated<br>hematology and<br>reticulocyte analyzer<br>for in vitro diagnostic<br>use in clinical<br>laboratories | Automated<br>reticulocyte counter<br>for in vitro diagnostic<br>use in clinical<br>laboratories |
| Sample Type | Whole blood | Whole blood | Whole blood |
| Sample Volume | 250µL Sampler mode<br>100 µL Manual mode<br>40µL whole blood for<br>capillary dilution | 250µL Sampler Mode<br>125µL Manual Mode<br>40µL whole blood for<br>capillary dilution | 100µL Sampler Mode<br>100µL Manual Mode<br>40µL whole blood for<br>capillary dilution |
| Performance | Similar to R-3000 and<br>RAM-I | Proven performance;<br>see #K964375 | Proven performance;<br>see #K912494 |
| Parameters | RET%, RET#, RBC#,<br>IRF, LFR, MFR,<br>HFR, PLT | RET%, RET#, RBC#,<br>IRF, LFR, MFR,<br>HFR, PLT | RET%, RET#, RBC#,<br>IRF, LFR, MFR, HFR |
| Reagents | RETSHEATH,<br>RETSEARCH diluent<br>and dye | Same | Same |
| Principles | Flow cytometry using<br>argon laser,<br>Auramine-O dye,<br>sheath flow.<br>Detection of forward<br>fluorescence and<br>scatter | Same | Same |
| Dimensions<br>(HxWxD) (mm) | 720x630x505 | 720x400x505 | 645x600x618 |
| Weight (kg) | 85.5 | 50 | 66 |
| QC System | Levy-Jennings,<br>SD,CV<br>15 Files per<br>Parameter, 180data<br>points per file | Levy-Jennings,<br>SD,CV<br>12 Files per Parameter<br>180data points per<br>file | Levy-Jennings,<br>SD,CV<br>6 Files per Parameter,<br>60 data points per file |
| Bar Code | Yes | Yes | Yes |
| No. of Test per Hour | Approximately 120 | Approximately 80 | Approximately 60 |

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## X. COMPARISON TO PREDICATE DEVICE

Data to support substantial equivalence to the predicate device were generated during correlation studies performed at our research center. In these studies, the following comparative performance evaluations were conducted using the proposed device and the predicate device to evaluate specimens from apparently healthy individuals and from patients with different pathological conditions which are expected to affect the results for particular parameters. Refer to Table 2 for a summary of the correlation studies.

| Parameter | n | r | r2 | Regression Equation |
|-----------|-----|-------|-------|---------------------|
| RET# | 487 | 0.994 | 0.988 | y = 0.965x + 0.001 |
| RET% | 487 | 0.997 | 0.994 | y = 0.964x + 0.051 |
| RBC | 486 | 0.998 | 0.997 | y = 1.009x - 0.072 |
| IRF | 486 | 0.956 | 0.913 | y = 0.948x + 1.409 |
| LFR | 486 | 0.956 | 0.913 | y = 0.948x + 3.819 |
| MFR | 486 | 0.923 | 0.852 | y = 0.917x + 1.433 |
| HFR | 486 | 0.954 | 0.910 | y = 0.940x + 0.490 |
| Platelet | 482 | 0.994 | 0.989 | y = 0.937x + 10.619 |

| Table 2 |
|------------------------------------------------------------------|
| Summary of Method Comparison Studies between<br>R-3500 and RAM-1 |

#### XI. HAZARD ANALYSIS:

A copy of the hazard analysis is provided as Attachment 8 of this submission.

#### XII. APPLICANT ADDRESS:

Sysmex Corporation Gilmer Road 6699 RFD Long Grove, IL 60047-9596

#### CONTACT PERSON: XIII.

Cathy Trester, MT(ASCP), Clinical Regulatory Specialist Clinical and Regulatory Affairs Sysmex Corporation Gilmer Road 6699 RFD Long Grove, IL 60047-9596 Phone: [phone] FAX: Internet: [e-mail]

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# XIV. MANUFACTURING FACILITY:

TOA Medical Electronics Co. Ltd. Japan Kobe, Japan

.

### SOFTWARE CERTIFICATION XVI.

A copy of the software certification is included as Attachment 9.

,

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Image /page/6/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's emblem, which is a stylized representation of a human figure embracing a sphere. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the emblem.

#### NOV 3 1998

Ms. Catherine Trester, MT (ASCP) Clinical and Requlatory Affairs SYSMEX™ Corporation Gilmer Road, 6699 RFD Long Grove, Illinois 60047-9596

Re : K981950 | SI Sysmex™ R-3500 Automated Reticulocyte Analyzer Trade Name: Requlatory Class: III Product Code: GKL Dated: Auqust 19, 1998 Received: August 20, 1998

Dear Ms. Trester:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual reqistration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 A substantially equivalent determination assumes compliance to 895. with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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Page 2

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a leqally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the requlation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number [phone] or [phone], or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radioloqical Health

Enclosure

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510(k) Number (if known):

Device Name: Sysmex ™ Automated Reticulocyte Analyzer R-3500

### Indications For Use:

The intended use of the Sysmex R-3500 is as a fully automated reticulocyte analyzer for in vitro diagnostic use in clinical laboratories.

## (PLEASE DO NOT WRITE BELOW THIS LINE- CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CHRD, Office of Device Evaluation (ODE)

(Division Sign-Off)

Division of Clinical Laboratory Devic 510(k) Number

**Presription Use**
(Per 21 CFR 801.109)

OR

Over-The-Counter Use __

(Optional Format 1-2-96)

000011

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